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The Efficient Science Hypothesis

January 30, 2017

This post is somewhat unusual by the standards of Biopolyverse. Its inspiration lies in a book called Connectome, by Sebastian Seung, but does not dwell on the central theme of this excellent and well-written volume (the nature and significance of the patterns of human neural connectivity). It rather picks up and runs with what is, in the context of the book as a whole, a mere aside to the general reader.

So just what is the Efficient Science Hypothesis? Seung based his brief proposal on the Efficient Market Hypothesis, and for a definition of that in turn, I provide one given online within Investopedia:

The efficient market hypothesis (EMH) is an investment theory that states it is impossible to “beat the market” because stock market efficiency causes existing share prices to always incorporate and reflect all relevant information. According to the EMH, stocks always trade at their fair value on stock exchanges, making it impossible for investors to either purchase undervalued stocks or sell stocks for inflated prices. As such, it should be impossible to outperform the overall market through expert stock selection or market timing, and that the only way an investor can possibly obtain higher returns is by purchasing riskier investments.

The Efficient Science Hypothesis (ESH) is thus an analogy of this economic proposal in the world of scientific endeavor, where it can be simply framed in terms of the scientific information and tools that are generally known and available. If the ESH is in fact correct, a single researcher or group cannot ‘beat the market’ by getting a leading advantage over others by using freely available materials and knowledge. Their competitors will be equally able to exploit what is on hand, and will be just as capable of devising the necessary experiments to unravel currently unsolved scientific problems. Thus, science will advance at a similar rate irrespective of who first makes a discovery by a marginal time factor, and irrespective of the specific players. (Should any specific individual or group be suddenly eliminated by some disaster, science as a whole will not be much retarded for a noticeable time). Throwing money, people, and hard work at a problem may get you ahead momentarily, but not for very long in scientific arms races between competitors on an equal footing from available technological and knowledge-based resources.

So the ESH would essentially propose.

Science to Technology and Back Again

A corollary of Seung’s ESH is the role of technology as a potential deal-breaker, or a means of beating the competition and thereby turning the tables on an otherwise level playing field. In this viewpoint, an individual or group who devise and implement a new technology that is applicable to their field of study will have, at least for a short period of time, an unassailable advantage over the rest. Within the analogy with the Efficient Markets Hypothesis, this kind of boost would correspond to some special insight into market conditions, without necessarily invoking unethical insider trading.

Of course, if the ESH was universally applicable in a very general sense, then as soon as a new technology was practically feasible (through the advent of previous technologies), then it would be rapidly and independently latched onto by the relevant international research community. In other words, a new technology would be ‘efficiently’ conceived and developed by independent workers as soon as it was enabled by the current ‘state of the art’, as patent attorneys would phrase it. And once again, no single individual or group would be able to surge ahead of their competitors.

Sometimes, it does seem as though this is indeed the case. Consider an example in this regard, where the central technology is the polymerase chain reaction (PCR), a ubiquitous process in molecular biology. Essentially, PCR involves the amplification of DNA strands through successive cycles of annealing of specific DNA primers (oligonucleotides) with a desired complementary template, enzymatic extension from the primers with a thermoresistant DNA polymerase, and thermal denaturation of the resulting duplex strands in order for the cycle to resume. Application of PCR thus allows potentially even a single DNA molecule to be amplified millions of times. Within the framework of this core amplification technology, which has been available and universally disseminated since the mid-1980s, many workers around the world seized upon its potential applications in an variety of circumstances. In 1990, at least four separate reports were published for essentially the same PCR application, where a hitherto unknown sequence specificity for a DNA-binding protein can be defined. (Prior to this, a protein could be shown to possess general DNA binding affinity, but testing whether it bound selectively in a sequence-specific manner, and (if so) defining the precise binding sequence, was often a difficult task). In a publication emerging in the following year dealing with a similar approach, the acronym CASTing (for Cyclic Amplification and Selection of Targets) was coined, and is most commonly applied to this technology. The details of this approach are not important in a discussion of the ESH, but an overview of it is provided in Fig. 1 for general background.

casting-techFig. 1. Outline of the CASTing process for defining the sequence specificity of a DNA-binding protein. An oligonucleotide is synthesized where a random tract (Nx, where typically x is around 20 bases in length) is flanked by defined sites for PCR primers. The complementary strands for the whole population are synthesized by extension from the ‘reverse’ primer, and the resulting duplexes are incubated with a DNA-binding protein of interest. Then, it is necessary to partition remaining free oligonucleotides from those which interact with the binding protein. This can be done in a variety of ways, including immunoprecipitation of the protein/complexes with specific antibody, gel electrophoresis, or by means of rendering the protein onto a solid-phase matrix and washing away unbound material. The partitioning process provides a subpopulation of oligonucleotides enriched for the binding site sequence of interest. This subpopulation is then amplified, and the process repeated through sufficient cycles (typically 6-10) to enable direct identification of binding sequences through cloning and sequencing. Confirmation of candidate sequences is then sought through direct binding assays.

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So this example can be raised in support of the ESH. Yet on closer inspection, as with CASTing. usually such convergent developments flow from an application of a particular pre-existing (though recent) technology. New technologies often have many applications beyond that which was initially aimed for. Advances of this kind could be categorized as ‘subtechnologies’ that spring from a core pre-existing technological structure. The ideas that are inherent in the original innovation, especially if it is revolutionary and widely used, have a high probability of occurring in many minds at the same time, thereby increasing the chances of convergent thoughts and co-incidental subtechnological advances. To use a very old phrase, one might say that such developments stem from ideas ‘whose time has come’.

Numerous additional examples can be cited concerning the proliferation of subtechnologies from a central technological advance. A vivid contemporary case in point is the seemingly endless applications of the CRISPR gene-editing technology, which in the space of a few years have emerged from multiple different laboratories. Beyond gene inactivation and editing, such downstream reworkings of CRISPR capabilities include the targeting of transcriptional activation or repression, RNA modulations, and epigenetic engineering processes. A full discussion of these is outside the scope of the present post.

Technology and Enablement

Technology builds on technology, and science advances with improved technological tools. This is depicted in Fig. 2 below, where a simple loop (A) can be broken down further, by indicating that a given technological development may lead directly to various subtechnologies (B; and as noted above), each of which can feed in turn back into the river of scientific development.

scitech-links

Fig. 2. Interactive loops between science and technology.

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Before a given technological development can be conceived and implemented, it is thus necessary that a body of theory and practice exists upon which the new invention can be built. Here we can look at the core technology for the above CASTing example, or the basic PCR approach itself. Fig. 3 shows a list (not necessarily exhaustive) for both knowledge-based items (basic science) and the technological background which underpin the PCR technique. Combined, these prior developments enable the implementation of the outgrowth PCR advance, and thus in turn PCR-based subtechnologies, such as the above CASTing example.

pcr-enablement

Fig. 3. Knowledge and prior technologies enabling the development of the Polymerase Chain Reaction (PCR).

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Still, even when all the various enabling bits and pieces are on hand, it still takes a human mind to join up the dots and formulate a new technological or scientific advance. Although Kary Mullis is acknowledged as the originator of PCR, it is notable that the conceptual basis of PCR cycling was described well over a decade earlier by Har Khorana’s group, but before some of the key enabling factors for PCR (Fig. 3) were readily available.

Many Minds and Many Labs Converging Towards a ThrESHold?

Taking a broad historical view, even when all necessary enabling components appear to be available, in some circumstances an advance does not occur for long periods of time. In an interesting essay, Jared Diamond noted that several areas of scientific progress could actually have occurred in ancient times, if people with the appropriate mind-set had acted accordingly. The fields of study that were potentially compatible with such early investigations included the classification of species, biogeography and comparative linguistics. So here the potential for considerable advancement of knowledge existed in the presence of ‘equal opportunity’ natural resources and general background information, but was never acted on.

Yet this does not directly conflict with the ESH, by simply pointing to the ‘S’ within the acronym. Where a general framework of systematic scientific investigation is lacking, no science is performed in the modern sense, efficiently or otherwise. The ancient Greeks, for example, indulged in plenty of speculations about the nature of things, but were not inclined to collect data or experiment. Still, even though no scientific tradition or infrastructure was in place, it is formally possible that a lone genius in those far-off times might have pioneered one of these possible lines of proto-scientific studies, and even founded the beginnings of systematic ‘natural philosophy’, as science itself was once termed.

It certainly could be argued that leaving aside the lack of any scientific tradition, there are many cultural features that would have had strong influences on the likelihood that any talented individual could have succeeded in a proto-scientific endeavor. For example, the opportunities for such activities among nomadic wanderers or impoverished subsistence cultures would have been virtually non-existent. But this raises another issue relevant to the ESH: the population size of participating individuals. This is simply based on the reasonable premise that the probability of a key innovating individual emerging is directly proportional to the available population base. Of course, within any ‘favorable’ culture only a small proportion of the populace in turn would be ‘available’ as potential innovators.

In ancient times, the global population was much less than now, and clearly even a generous assignation of cultures (and their internal elites) that could conceivably enable the genesis of scientific undertakings would reduce the ‘available’ population pool much more. There is another factor, implicit within the ESH but crucially important to it, that is also very relevant to these ‘ancient science’ considerations: communication. In order for any version of the ESH to exist, dissemination of scientific findings must be made as rapidly as possible. Where writing and copying themselves are highly rate-limiting steps, and lines of communication are poor if present at all, clearly no ‘ancient ESH’ could have been viable.

So from the ancient world we bounce back to modern times, where the population base of relevant individuals is immensely higher, and where communication via the internet is all but instantaneous. If we imagine an ‘ESH Threshold’ (or ThrESHold for short) as needing a requisite population size and communication rate to be attained, then have we already converged to this point?

Certainly if it was agreed that scientific progress in the modern world is most likely to have a uniform trajectory, through widespread parity of researchers in terms of skills and background knowledge, then the ESH would be applicable. But what about revolutionary developments emerging from the minds and hands of super-gifted individuals?

Individuals and Serendipity

Major scientific advances have historically been made by individuals, not groups. Innovations in the past have stemmed from specific minds, giving themselves a leading edge over competitors of the day. For a long time, the classic ‘Why Didn’t I Think of That?’ (WDITOT) effect prevailed – where an idea is a relatively straightforward combination of two or more pieces of knowledge that were freely available at the time of its conception, but only put together initially by a single individual. (And where many contemporaries rue their lack of comparable insight after the fact). Where a relatively small population base of possible participants existed, the WDITOT effect had a reasonably high probability of occurring. Yet as the ThrESHold is approached with an increasing participating population and better communications, the likelihood of discoveries occurring only through single-individual eureka moments diminishes accordingly in favor or multiple contemporaneous discovery events.

It might be conceded that for some ‘timely’ innovations, many modern minds are primed to develop them at more or less the same juncture. Yet what about the real quantum leaps requiring stunningly original insights? Surely a uniform field of progress along the lines of the ESH would not apply there? In principle, this would seem to be the case, but it is not clear that such stand-out events have been occurring as they did in past. Thus, it has been a common question of many people to ask, “Why are there no more Einsteins? (or where are they, or some variation on this theme). A number of different answers to this have been proffered, including the notion that it’s simply much harder for anyone (no matter how smart) to make a revolutionary contribution, since all the low-hanging fruit of humanity’s quest for knowledge have already been picked. Another answer suggests that it’s wrong to think there are no more Einsteins, since there are in fact many in contemporary research, making it that much harder to stand out from the pack. Yet another point made in this regard is the supposition that bright young scientists who are most likely to have highly novel insights are too diverted into relatively mundane work in order to publish and establish their careers. If so, this would constitute a novel ‘cultural factor’ limiting innovations and ground-breaking work that could be made, even if one assumes that the ‘raw material’ of knowledge that could enable new breakthroughs already exists. (This is by analogy with the above note regarding the limitations of ancient science by cultural imperatives, and suggests that such effects many not be entirely discountable in the present day).

And then there is the matter of serendipity, where a chance-based observation can lead to a hitherto unprecedented line of investigation, or on occasion a dramatically radical insight that leaps over conventional thought. Surely this kind of development is a wild-card event that cannot be accommodated by the smoothing effect of the ESH? Certainly in general, an advance-by-chance could in principle provide a group with a lead in a field, perhaps analogously to an entirely fortuitous market investment, to use the original inspiration for the ESH in terms of market efficiency. But in a world at or past the ThrESHold, even serendipitous discoveries may be influenced by the scientific zeitgeist. Consider a contemporary scientific problem which is being investigated globally, and for which a limited number of experimental pathways are available. Given this, there is a high probability that a specific line of experiments will be undertaken by multiple independent groups, and experimental steps which afford the opportunity of leading to a serendipitous and unexpected observation will be likewise performed independently. With that background, it is then down to the experimental observer as to whether he or she will pick up on the novel observation and ‘run with it’. Here we can be reminded of the famous aphorism attributed to Pasteur, “Fortune favors the prepared mind”.

Of course, this scenario only applies to a subset of possible serendipitous opportunities, excluding cases where a truly unpredictable event such as a laboratory accident provided the key observations. Even that might tend to be smoothed out to some extent if the participating population is sufficiently large, but attaining such population numbers on a finite planet seems exceedingly unlikely.

Conclusions

If the ESH applies, then the proposition that a technological advance is a way to temporarily escape the smooth landscape of progress falls down, since a technological innovation itself is highly likely to emerge repeatedly and independently when times are ripe (as exemplified with the CASTing example above).

As the global pool of workers engaged in science and technology grows, so does the likelihood that parallel discoveries will be made. So the growth of the collective pool of investigators in specific fields will tend to reach a threshold (the ‘ThrESHold’) that converges with an approximation of state of affairs as postulated by the ESH. Nevertheless, individual genius and at least some forms of serendipity provide opportunities for a temporary leap-frogging of the consensus approach to advancement of a particular field.

Finally, we can make note of ‘temporary’ caveat above. A scientific ideal is the publishing and dissemination of results, but this is very far from merely an unworldly principle to those confronted with the ‘publish or perish’ attitude to scientific career promotion. So an individual career may be enhanced by timely publication of revolutionary results, but the field as a while will be able to profit from the advance involved. In this sense, any deviation from the ESH is soon ‘corrected’ by knowledge dissemination. An important exception is clandestine research carried out by governments with military or state security potential, where an advance edge may have far-reaching repercussions. Even here, though, with the passage of time such scientific secrets tend to be disseminated one way or the other.

There we will leave it, but with a final biopoly-verse salute to the wild-card elements by which the smooth progress of Efficient Science may be for a brief time by-passed:

So does science move in a dance

With the latest techno-advance?

But what of the dreamers

The players, the schemers,

Who stumble on things by mere chance?

References & Details

(In order of citation, giving some key references where appropriate, but not an exhaustive coverage of the literature).

‘……a book called Connectome, by Sebastian Seung…..’ In full, the title is Connectome: How the Brain’s Wiring Makes Us Who We Are; Mariner Books, 2013.

‘…… at least four separate reports were published for essentially the same PCR application……’ These are: Blackwell et al. 1990; Mavrothalassitis et al. 1990; Thiesen & Bach 1990 and Pollock & Treisman 1990.

‘…….the acronym CASTing (for Cyclic Amplification and Selection of Targets) was coined, and is most commonly applied to this technology…..’     See Wright et al. 1991. Despite the priority of the above 1990 reports, the CASTing acronym may have trumped alternatives due to its catchy appeal, and its evoking throwing a net into a sea of sequences in order to find the desired one.

‘……..it still takes a human mind to join up the dots…..’     Perhaps not for much longer, at least in some circumstances, given the rapid progress in recent times of neural-net based machine-learning artificial intelligence.

‘……Kary Mullis is acknowledged as the originator of PCR…..’     See Saiki et al. 1985, and Mullis 1990, for a personal account of his discovery. The initial PCR reports did not use a thermostable DNA polymerase as listed in Fig. 3, but all the full potential of PCR was not realized until heat-resistant polymerases from thermophilic organisms (such as Taq polymerase) began to be used. Mullis received a Nobel Prize for the PCR innovation in 1993.

‘……the conceptual basis of PCR cycling was described well over a decade earlier by Har Khorana’s group……’     See Kleppe et al. 1971. Ironically, Khorana was a major contributor to the development of practical oligonucleotide synthesis, which is an essential enabling technology for PCR. He had already received a Nobel Prize (in 1968 for work associated with unraveling the genetic code) before this paper was published.

‘………Jared Diamond noted that several areas of scientific could actually have occurred in ancient times…..’     See Diamond, J. in This Idea Must Die (p. 486; 2015, John Brockman, Ed.).

‘……it’s wrong to think there are no more Einsteins, since there are in fact many in contemporary research……’     This kind of proposition was made by James Gleick, in his biography of Richard Feynman (as cited in a Scientific American blog).

‘……bright young scientists who are most likely to have highly novel insights are too diverted into relatively mundane work…..’ This has been raised by the prolific science writer Philip Ball, in an article in The Guardian.

Next post: June.

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